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Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis

J Fransen¹, R F J M Laan¹, M A F J van der Laar², T W J Huizinga³, P L C M van Riel¹

¹ Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, Netherlands
² Department of Rheumatology, Medisch Spectrum Twente, Enschede, Netherlands
³ Leiden University Medical Centre, Leiden, Netherlands

Correspondence to:
Correspondence to:
Dr J Fransen
Department of Rheumatology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands; j.fransen{at}reuma.umcn.nl

Objective: To study the influence of rheumatologists’ adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis.

Methods: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis.

Results: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean –0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups.

Conclusions: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.

Abbreviations: ACR, American College of Rheumatology; DAS, disease activity score; DMARD, disease modifying antirheumatic drug; EULAR, European League Against Rheumatism; RAI, Ritchie articular index; RCT, randomised controlled trial; TNF, tumour necrosis factor ; VAS, visual analogue scale

Keywords: rheumatoid arthritis; methotrexate; outcome

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